ABSTRACT Fluorescence sensing in the near‐infrared‐II (NIR‐II, 1000–1700 nm) window can provide reliable physiological information. However, designing such probes is highly challenging, as most existing NIR‐II fluorophores lack modifiable fluorescence regulatory sites and are easily quenched in physiological environments. Herein, we introduce modifiable electron‐donating dimethylamino groups to develop a NIR‐II aggregation‐induced emission (AIE) sensing platform termed NBBT. The scaffold hopping strategy avoids the commonly used bulky rotors, enhancing molecular rigidity and electronic conjugation while preserving the AIE property, as confirmed by single‐crystal analysis and theoretical calculations. NBBT overcomes the quenching effect, achieves a four‐fold increase in photoluminescence quantum yield, and enables clear in vivo vascular imaging. Further functionalization yields two NIR‐II probes, pH‐responsive NBBT‐H and ROS‐responsive NBBT‐B. NBBT‐B can reflect the inflammation degree in lipopolysaccharide‐induced subcutaneous inflammation and acetaminophen‐induced liver injury in vivo. Overall, our work provides a facile approach to developing NIR‐II probes for biosensing and reveals the effectiveness of scaffold hopping in designing functional organic aggregates.
Shen et al. (2026) studied this question.